Vitamin D Deficiency in Dialysis Patients: Effect of Dialysis Modality and Implications on Outcome

Article Outline

• Abstract
• Patients and Methods
  • Patients
  • Biochemical Analysis and Other Measurements
  • Statistical Analyses
• Results
  • General Characteristics
  • Univariate Correlates of 25(OH)D in HD Patients
  • Determinants of 25(OH)D Deficiency in HD Patients
  • 25(OH)D and Mortality
• Discussion
• Acknowledgments
• References
• Copyright

Objective

Vitamin D deficiency has been linked to cardiovascular disease and mortality in hemodialysis (HD) patients. The purpose of the present cross-sectional study was to analyze the Vitamin D status of dialysis patients from a single center, study determinants of Vitamin D deficiency, and assess its implications on outcome.

Methods

A prospective observational study of 115 prevalent dialysis patients was carried out, in which clinical and dialysis-related characteristics including routine biochemistry were studied in relation to levels of 25-hydroxyvitamin-D (25[OH]D, chemiluminescence). Survival was assessed after a median follow-up period of 413 days.

Results

25(OH)D deficiency and insufficiency was present in 51% and 42% of the patients, respectively. Only 7% of the patients showed normal 25(OH)D levels. Peritoneal dialysis patients presented the lowest 25(OH)D levels. Also, a significant difference was found between on-line hemodiafiltration (OL-HDF) and conventional HD (11 [6 to 16] versus 19 [13 to 27] ng/mL; P < 0.001; 25th to 75th percentiles, conventional HD versus OL-HDF respectively). In multinomial logistic regression analysis, patients on conventional HD had 8.35 greater odds (95% CI [2.04 to 34.20]) of 25(OH)D deficiency than OL-HDF even after adjustment for sex, parathyroid hormone, pH, and Charlson comorbidity index. During the follow-up period, 18 patients died. Both crude and adjusted (hazard ratio, 6.96; 95% CI [1.44 to 33.64]) Cox analysis identified 25(OH)D deficiency as a mortality risk factor.

Conclusion

This observational study underlines the high prevalence of hypovitaminosis D in dialysis patients and its strong implications on outcome. Furthermore, our results suggest that OL-HDF was associated with a better preservation of the vitamin D status as compared with conventional HD.

CHRONIC KIDNEY DISEASE (CKD) is a public health problem associated with very poor outcomes,¹, ² mainly because of cardiovascular-related causes.³ At present, the reasons for the CKD increased mortality risk are not fully elucidated, as several large randomized controlled trials have consistently been unable to show a survival benefit of new treatment strategies.⁴ Apart from considering traditional risk factors such as age, hypertension, diabetes, and hypercholesterolemia, there is increasing evidence that abnormalities in mineral metabolism contribute to the increased morbidity and mortality in patients receiving dialysis.⁵, ⁶, ⁷

Vitamin D, especially the active form 1,25-dihydroxycholecalciferol and its analogues, has traditionally been used to prevent and treat secondary hyperparathyroidism in CKD patients. However, several studies have pointed to the high prevalence of vitamin D deficiency as measured by its precursor 25-hydroxyvitamin-D (25[OH]D)⁸, ⁹ and suggest that, beyond its effect on parathyroid hormone (PTH) and divalent ion homeostasis, 25(OH)D levels, vitamin D replacement may affect both disease progression toward end-stage renal disease (ESRD) and survival.¹⁰, ¹¹, ¹² The reasons for this effect are not yet completely understood, but it may relate to the capacity of vitamin D to promote vascular endothelial health, improve arterial dysfunction, and modulate not only the immune and the inflammatory cascade, but also the renin-angiotensin system.¹³

Because CKD per se was an independent predictor of vitamin D deficiency in the National Health and Nutrition Examination Survey (NHANES) III study,¹⁴ it has been hypothesized that certain conditions associated with CKD, such as urinary or dialysis protein loss or the decreased food intake, can predispose these patients to hypovitaminosis D.¹⁵ For instance, peritoneal dialysis (PD) patients may have greater vitamin D losses,¹⁶, ¹⁷ but there is still little knowledge about other determinants of hypovitaminosis D in ESRD patients. The purpose of the present cross-sectional study was to analyze the vitamin D status of a single center in Spain, study possible determinants of vitamin D deficiency, and assess its implications on outcome.

Back to Article Outline

Patients and Methods 

Patients 

This study included all prevalent patients (n = 115) on maintenance dialysis at the Severo Ochoa University Hospital, Madrid, Spain. Patients were clinically stable (mean age, 60 ± 16 years), and had a median preceding time on dialysis (vintage time) of 27.5 (12.0 to 70.5) months. All patients were invited to participate, and all accepted and were included in the study. Recruitment and sampling were done from November 12, 2007 until December 20, 2007. Signed informed consent was obtained from all patients before inclusion in the study.

Survival was determined from the day of examination until February 15, 2009, with a median follow-up period of 413 (interquartile range, 412 to 414) days. There was no loss to follow-up of any patient.

A total of 94 (81%) underwent either conventional hemodialysis (HD; n = 61) or on-line hemodiafiltration (OL-HDF; n = 33) for at least 4 hours, 3 times a week, using ultrapure water the quality of which was evaluated monthly by the kinetic chromogenic limulus amebocyte lysate test. The dialysate concentration of calcium was 1.75/1.5 mmol/L. Twenty-one patients (19%) were treated either by continuous ambulatory PD (n = 9) or automated PD (n = 12), using biocompatible glucose-based and icodextrin-based solutions. The causes of ESRD were chronic glomerulonephritis (18%), interstitial nephritis (14%), polycystic kidney disease (6%), hypertensive nephroangiosclerosis (19%), diabetic nephropathy (19%), idiopathy (11%), and other causes (12%). A history of comorbidities was recorded for each patient and scored according to Charlson et al.¹⁸ Thirty-two patients were diabetic (28%) and 43 patients (37%) presented a clinical history of cardiovascular disease. Sixty (53.6%) patients were taking active forms of vitamin D, including paricalcitol, alphacalcidol, or calcitriol. None of the patients were receiving any other form of vitamin D supplementation. Phosphate binders were prescribed to 95 patients (82%). Thirty-three patients (28 %) were consuming calcium-containing phosphate binders, whereas 40 (35 %) were on sevelamer, and 59 (51 %) on aluminum-containing phosphate binders. Twenty-two patients (19%) were taking calcimimetic treatment with cinacalcet.

Biochemical Analysis and Other Measurements 

Blood samples were taken from the patients in fasting condition just before the second dialysis session of the week. After 20 to 30 minutes of quiet resting in semirecumbent position, samples were taken into chilled vacutainers, placed immediately on ice, centrifuged at 4°C, and the serum stored at −40°C before assay. Measurements of serum creatinine, pH, Ca, P, albumin, bone alkaline phosphatase, and 25(OH)D were analyzed using certified methods at the Department of Laboratory, Severo Ochoa University Hospital, Madrid, Spain. Total Ca was corrected for serum albumin using the equation: Calcium = Ca + 0.8 (4 − albumin). Serum PTH was measured by chemiluminescence (reference values for PTH: 16 to 87 pg/mL). Levels of 25(OH)D (including both 25OHD3 and 25OHD2) were determined by a commercial chemiluminescence assay (DiaSorin LIAISON, Stillwater, MN). The reference values for 25(OH)D were 8 to 60 ng/mL, and the coefficient of variation intra-assay were 7.7% to 12% at levels 5.8 to 35 ng/mL. Inter-assay coefficient of variation values were 11.6% to 25% at levels 5.8 to 35 ng/mL. An erythropoietin (EPO) resistance index (ERI) was defined as the weekly EPO dose (U/kg predialysis body weight per dose) divided by Hb level (g/dL). The so called dry body weight of the patients was measured immediately after the dialysis session.

Statistical Analyses 

Statistical analyses were performed using statistical software SAS version 9.1.3 (SAS Campus Drive, Cary, NC). Normally distributed variables were expressed as mean ± standard deviation, and non-normally distributed variables were expressed as median and range (minimum and maximum) or interquartile range (25th to 75th percentile). Also, categorical values were expressed as numbers and percentages. Statistical significance was set at the level of P < .05. Comparisons between 2 groups were assessed with the Mann–Whitney or χ² test. Differences among more than 2 groups were analyzed by the Kruskal–Wallis test. Because many values were not normally distributed, Spearman's rank correlation (ρ) was used to determine univariate correlations between 25(OH)D and selected parameters. Multivariate associations were performed by multinomial logistic regression analyses when studying the determinants of 25(OH)D deficiency in the HD population. The range of deficient, insufficient, and normal vitamin D levels were established according to the current Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines¹⁹ as follows: mild deficiency, 5 to 15 ng/mL; insufficiency, 15 to 30 ng/mL; normal levels, >30 ng/mL. Survival analyses were made with the Kaplan–Meier survival curve or the Cox proportional hazard model. The relative risks for mortality were determined by multivariate Cox regression analysis, and presented as hazard ratio (95% CI).

Back to Article Outline

Results 

General Characteristics 

This study sample included 115 prevalent patients from a single center: 61 patients were maintained on conventional HD, 33 were on OL-HDF, and the remaining 21 were onPD. Baseline characteristics of these patients according to the dialysis technique are shown in Table 1. Although the patient groups had similar proportions of males, diabetes, or cardiovascular disease, PD patients tended to be younger and presented with a lower comorbidity risk and better nutritional status. Regarding the different HD techniques, OL-HDF patients were younger, presented with less comorbidities and larger percentage of fistulas than catheters. A nonsignificant trend toward longer vintage time (preceding time on dialysis) in OL-HDF patients was observed.

Table 1. General Characteristics of 115 Prevalent Dialysis Patients From a Single-Center Subdivided According to Dialysis Techniques

PTH, parathyroid hormone; ERI, EPO resistance index; ns, no significance.

Data are expressed as median (range), mean ± SD, or percentage as appropriate.

According to the K/DOQI guidelines,¹⁹ only 7% of the patients had normal 25(OH)D levels (Fig. 1; >30 ng/mL), 42% had insufficient levels (15 to 30 ng/mL), and 51% presented levels considered to be mild deficient (5 to 15 ng/mL). No patient was found with severe deficiency (<5 ng/mL). The lowest levels of 25(OH)D were found in the PD patients. Interestingly, 25(OH)D levels were reduced almost by half in patients treated with conventional HD as compared with those being treated with OL-HDF (Fig. 2). As previous reports have already demonstrated that more 25(OH)D is removed by PD than by HD,¹⁶, ¹⁷ we focused our further analyses on the 2 HD modalities only.

• 
  • View Large Image
  • Download to PowerPoint

• Figure 1 

  Distribution of vitamin D levels among 115 prevalent dialysis patients. Vertical dotted lines delineate the range of deficiency (5 to 15 ng/mL), insufficiency (>15 to 30 ng/mL), and normal (>30 ng/mL) vitamin D levels according to the current KDOQI guidelines.¹⁹

• 
  • View Large Image
  • Download to PowerPoint

• Figure 2 

  25(OH)D levels according to dialysis technique in 115 prevalent dialysis patients. The 25(OH)D levels were lower in PD patients as compared with hemodialysis patients (on-line hemodiafiltration [OL-HDF] and conventional hemodialysis [HD] combined). At the same time, 25(OH)D levels were significantly higher in patients treated by OL-HDF as compared with those treated by conventional HD.

Univariate Correlates of 25(OH)D in HD Patients 

We used Spearman Rank's correlation test to assess univariate correlates between 25(OH)D and selected parameters in the HD population. We did not observe any correlation with age, serum phosphorus, calcium, albumin, prealbumin, or C-reactive protein. However, 25(OH)D levels were negatively correlated with PTH (Fig. 3) and the ERI (ρ = −0.24. P = < .05) as well, and there was a positive correlation with pH and 25(OH)D (Fig. 3). At the same time, 25(OH)D levels were more elevated in men as compared with women (16.5 [1 to 26] ng/mL versus 9.5 [6 to 16] ng/mL; P = .001; n = 55/39), and in patients with low versus high Charlson comorbidity risk (16.5 [10 to 25] ng/mL versus 11.5 [6 to 17] ng/mL; P = .02; n = 52/42; high risk defined as comorbidity score ≥7).

• 
  • View Large Image
  • Download to PowerPoint

• Figure 3 

  Spearman's Rank correlation test between 25(OH)D and parathyroid hormone (PTH; Panel A) and pH (Panel B).

Determinants of 25(OH)D Deficiency in HD Patients 

Clinical and phenotypical characteristics of HD patients were analyzed according to the clinical cutoff point 15 ng/mL of 25(OH)D, a level thought to represent 25(OH)D deficiency (Table 2). The 25(OH)D deficient patients were more often women, showed higher PTH serum levels, higher Charlson comorbidity index, and a trend toward a more acidotic state. Also, patients on conventional HD were more likely to be 25(OH)D deficient as compared with OL-HDF patients. The proportion of patients having high flux membrane was not different between the groups.

Table 2. Clinical Characteristics of 94 Prevalent HD Patients According to the Presence or Absence of Vitamin D (25[OH]D) Deficiency

ns, no significance; PTH, parathyroid hormone; ERI, EPO resistance index.

Data are expressed as median (range), mean ± SD, or percentage as appropriate.

To assess whether the HD technique may relate to this insufficiency independent of confounders, we performed a logistic regression analysis with 25(OH)D deficiency as the dependent variable (Table 3). We included possible confounders such as sex, PTH, pH, and Charlson comorbidity index. Results showed that in this model female gender, pH <7.35, and conventional HD were independently associated to bigger odds of being 25(OH)D deficient, PTH <150 pg/mL appeared as an advantage.

Table 3. Odds Ratios (ORs) and 95% CI for the Presence of 25(OH)D Deficiency Among 94 Prevalent HD Patients

Output from a logistic regression analysis. The reference category for PTH value was 150 to 300 pg/mL. The adjusted r² of the model was 0.42. Vitamin D deficiency was defined as a level of 25(OH)D < 15 ng/mL.

25(OH)D and Mortality 

Survival was determined after a median follow-up of 413 (412 to 414) days. In this period, 20 fatal events occurred, 18 of which affected the HD patients (both conventional HD and OL-HDF together). The causes of death were starvation (9 deaths, 50%), cardiovascular failure (5 patients, 28%), and infectious complications (4 patients, 22%). At baseline, 25(OH)D levels of those who died were significantly lower than those who survived (10 [6 to 14] ng/mL versus 16 [9 to 24] ng/mL; P < .01). Kaplan–Meier analysis showed that 25(OH)D deficient patients were at increased risk of dying (Fig. 4). We used the Cox proportional hazards model to adjust for possible confounders in this association (Table 4). Results showed that 25(OH)D deficient patients were at increased risk of dying even after adjustment for age, sex, ERI, diabetes mellitus, and cardiovascular disease.

• 
  • View Large Image
  • Download to PowerPoint

• Figure 4 

  Kaplan–Meier according to 25(OH)D insufficiency in 115 prevalent dialysis patients.

Table 4. Adjusted Relative Risk of All-cause Mortality in 94 Prevalent HD Patients

	Hazard Ratio	P
Crude
25(OH)D, <15 ng/mL	4.16 (1.19-14.54)	.02
Adjusted
25(OH)D, <15 ng/mL	6.96 (1.44-33.64)	.01
Age (years)	1.05 (1.01-1.10)	.03
Sex (male)	0.38 (0.12-1.20)	.09
ERI, >20 IU/kg/week/hb	5.27 (1.37-20.31)	.01
Diabetes mellitus, present	1.20 (0.35-4.05)	.7
Cardiovascular disease, present	1.47 (0.44-4.89)	.5

Back to Article Outline

Discussion 

The present observational study underlines the high prevalence of hypovitaminosis D in dialysis patients, and its negative effect on outcome. Furthermore, our results also suggest that the different HD techniques may further influence 25(OH)D status. Specifically, OL-HDF was associated with a better preservation of the vitamin D status as compared with conventional HD, irrespective of a number of confounders. Limited by a low sample size and by the observational nature of our design, we hope to encourage further research on possible differences in vitamin D losses with respect to the various HD procedures. Should these results be confirmed in subsequent studies, it could represent a gateway toward the implementation of preventive measures against 25(OH)D losses.

To the best of our knowledge, this is the first Spanish report on the prevalence of vitamin D deficiency, as assessed by 25(OH)D in dialysis patients. It is especially alarming that only 7% of our prevalent dialysis patients showed normal vitamin D levels. In the general population, the status of vitamin D depends on many variables such as aging,²⁰ skin pigmentation,²¹ sun exposure,²² and therefore season and dietary intake.²³ Thus, whereas our results are in agreement with those of other South European countries with similar ultraviolet exposure and a Mediterranean dietary pattern,¹¹, ¹⁶ they are also similar to reports from the United States²⁴ and Denmark,²⁵ altogether suggesting that other factors inherent to ESRD or to the dialysis procedure may override these influences.¹⁵

In our sample population we found, not unexpectedly, that 25(OH)D levels were lower in women and in patients with history of comorbidities.¹¹, ²⁴, ²⁶ Although we measured few markers of nutritional status or dietary intake, 25(OH)D levels correlated with dry body weight, indirectly supporting the postulate that hypovitaminosis D could be, in part, a result of poor appetite in CKD.¹⁵, ²⁷, ²⁸ Also, vitamin D deficiency tended to associate with a more acidotic status as acidosis can contribute to negative calcium balance and to the development of skeletal demineralization.¹⁹ The mechanism behind the relationship between acidosis and low 25(OH)D levels is not clear, although some common pathway may lead to both acidosis and lower vitamin D intake or skin production.²⁹ Alternatively, acidosis itself might influence vitamin D levels through effects on 1-alpha hydroxylase activity.³⁰ However, much less is known about the regulation of vitamin D3 25-hydroxylase activity, partly because of the elusiveness of the cytochrome P450 isoforms responsible for this activity.³¹ In this regard, correction of acidosis by oral NaHCO₃ treatment in HD patients increased circulating 1,25-(OH)₂ Vit D3, but 25(OH)D levels were not measured in that study.³² Finally, low levels of PTH were linked to lower odds of vitamin D deficiency, in agreement with the demonstration that the parathyroid cell has the machinery to produce vitamin D locally from its precursor 25(OH)D and therefore, the deficiency or insufficiency of 25(OH)D could have contributed to the development of secondary hyperparathyroidism.³³

We also observed that patients undergoing PD showed the lowest 25(OH)D levels, linking to the various reports on increased loss of both 25(OH)D and vitamin D-binding protein in the dialysate.¹⁶, ¹⁷ In connection to this, our PD patients had the highest PTH levels and phosphate binders, as well as calcimimetics were more often prescribed to the PD patients than to the HD patients. However, one interesting finding in our study was that OL-HDF patients showed significantly higher 25(OH)D levels than patients treated with conventional HD. Although OL-HDF patients tended to be younger and therefore had less comorbidity and signs of better nutritional status with higher prealbumin levels, adjustment for these differences did not alter the results. Although we cannot exclude the effect of unknown or residual confounding factors like dietary intake or lifestyle factors, our study was not designed to discern how the technical differences between dialysis modalities could affect vitamin D metabolism. To the best of our knowledge, no studies have yet studied vitamin D clearance in HD patients treated with high versus low flux membranes or the effect of on-line regimes. 25(OH)D is a small sized molecule (<500 D)³⁴ that usually circulates bound to protein.³⁵ Because middle-sized protein-bound vitamins such as vitamin B12 proved to be as efficiently retained in OL-HDF as in conventional HD,³⁶ no difference in the clearance of 25(OH)D clearance between these HD techniques should, a priori, be expected.³⁷ Because OL-HDF has been associated to a better microinflammatory state,³⁸ a more efficient removal of uremic toxicity³⁹, ⁴⁰ and a lower cardiovascular incidence,⁴¹ we speculate on the existence of yet unknown indirect mechanisms by which 25(OH)D levels may be raised or preserved. For instance, a better leptin removal by OL-HDF⁴² may indirectly lead to improvement of the nutritional status through stimulation of feeding behavior and therefore favoring vitamin D intake.¹⁵, ²⁷

Finally, we could identify 25(OH)D deficiency as a mortality risk factor that persisted after adjustment of various confounders. While our results agree with big-cohort dialysis populations,¹⁰, ¹¹, ¹² the magnitude of the effect in a small material like ours strengthens the putative deleterious effects of hypovitaminosis D on the patient's outcome. In the last decade, the interference of vitamin D with the cardiovascular system has emerged as one of the most intriguing research areas in cardiovascular medicine.¹³ Our observational data makes the need for well-designed studies to study dialysis-related causes of vitamin D deficiency as well as for a randomized controlled study to prove a causal relationship between hypovitaminosis D therapy and improved survival in CKD patients.

Back to Article Outline

Acknowledgments 

Carolina Gracia-Iguacel was a visiting nephrologist in training at the Divisions of Renal Medicine and Baxter Novum, Karolinska Institutet, Sweden, coming from Severo Ochoa Hospital, Madrid, Spain. Baxter Novum is the result of an unconditional grant from Baxter Healthcare Inc to the Karolinska Institutet. The authors acknowledge the support of the Loo and Hans Ostermans foundation, Swedish Kidney Association, and Karolinska Institutets Centre for Gender Medicine.

Back to Article Outline

References 

1. Keith DS, Nichols GA, Gullion CM, et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164:659–663
   • View In Article
   • MEDLINE
   • CrossRef
2. Wen CP, Cheng TY, Tsai MK, et al. All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan. Lancet. 2008;371:2173–2182
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (285 KB)
   • CrossRef
3. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305
   • View In Article
   • CrossRef
4. Stenvinkel P, Carrero JJ, Axelsson J, et al. Emerging biomarkers for evaluating cardiovascular risk in the chronic kidney disease patient: how do new pieces fit into the uremic puzzle?. Clin J Am Soc Nephrol. 2008;3:505–521
   • View In Article
   • CrossRef
5. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol. 2001;12:2131–2138
   • View In Article
   • MEDLINE
6. Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006;70:771–780
   • View In Article
   • MEDLINE
   • CrossRef
7. Avesani CM, Carrero JJ, Axelsson J, et al. Inflammation and wasting in chronic kidney disease: partners in crime. Kidney Int. 2006;70(Suppl):S8–S13
   • View In Article
   • CrossRef
8. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71:31–38
   • View In Article
   • MEDLINE
   • CrossRef
9. Jean G, Charra B, Chazot C. Vitamin D deficiency and associated factors in hemodialysis patients. J Ren Nutr. 2008;18:395–399
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (120 KB)
   • CrossRef
10. Wolf M, Betancourt J, Chang Y, et al. Impact of activated vitamin D and race on survival among hemodialysis patients. J Am Soc Nephrol. 2008;19:1379–1388
    • View In Article
11. Ravani P, Malberti F, Tripepi G, et al. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int. 2009;75:88–95
    • View In Article
    • CrossRef
12. Wang AY, Lam CW, Sanderson JE, et al. Serum 25-hydroxyvitamin D status and cardiovascular outcomes in chronic peritoneal dialysis patients: a 3-y prospective cohort study. Am J Clin Nutr. 2008;87:1631–1638
    • View In Article
13. Michos ED, Melamed ML. Vitamin D and cardiovascular disease risk. Curr Opin Clin Nutr Metab Care. 2008;11:7–12
    • View In Article
    • CrossRef
14. Mehrotra R, Kermah D, Budoff M, et al. Hypovitaminosis D in chronic kidney disease. Clin J Am Soc Nephrol. 2008;3:1144–1151
    • View In Article
    • CrossRef
15. Cuppari L, Garcia-Lopes MG. Hypovitaminosis D in chronic kidney disease patients: prevalence and treatment. J Ren Nutr. 2009;19:38–43
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (104 KB)
    • CrossRef
16. Taskapan H, Ersoy FF, Passadakis PS, et al. Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis. Clin Nephrol. 2006;66:247–255
    • View In Article
    • MEDLINE
17. Shah N, Bernardini J, Piraino B. Prevalence and correction of 25(OH) vitamin D deficiency in peritoneal dialysis patients. Perit Dial Int. 2005;25:362–366
    • View In Article
    • MEDLINE
18. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–383
    • View In Article
    • MEDLINE
    • CrossRef
19. National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1–S201
    • View In Article
20. Sherman SS, Hollis BW, Tobin JD. Vitamin D status and related parameters in a healthy population: the effects of age, sex, and season. J Clin Endocrinol Metab. 1990;71:405–413
    • View In Article
    • CrossRef
21. Matsuoka LY, Wortsman J, Haddad JG, et al. Racial pigmentation and the cutaneous synthesis of vitamin D. Arch Dermatol. 1991;127:536–538
    • View In Article
22. Saraiva GL, Cendoroglo MS, Ramos LR, et al. Influence of ultraviolet radiation on the production of 25 hydroxyvitamin D in the elderly population in the city of Sao Paulo (23 degrees 34'S). Brazil. Osteoporos Int. 2005;16:1649–1654
    • View In Article
23. Vieth R, Cole DE, Hawker GA, et al. Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr. 2001;55:1091–1097
    • View In Article
    • MEDLINE
    • CrossRef
24. Wolf M, Shah A, Gutierrez O, et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int. 2007;72:1004–1013
    • View In Article
    • CrossRef
25. Ewers B, Gasbjerg A, Moelgaard C, et al. Vitamin D status in kidney transplant patients: need for intensified routine supplementation. Am J Clin Nutr. 2008;87:431–437
    • View In Article
26. Jean G, Terrat JC, Vanel T, et al. Daily oral 25-hydroxycholecalciferol supplementation for vitamin D deficiency in haemodialysis patients: effects on mineral metabolism and bone markers. Nephrol Dial Transplant. 2008;23:3670–3676
    • View In Article
    • CrossRef
27. Carrero JJ. Identification of patients with eating disorders: clinical and biochemical signs of appetite loss in dialysis patients. J Ren Nutr. 2009;19:10–15
    • View In Article
28. Chmielewski M, Carrero JJ, Stenvinkel P, et al. Metabolic abnormalities in chronic kidney disease that contribute to cardiovascular disease, and nutritional initiatives that may diminish the risk. Curr Opin Lipidol. 2009;20:3–9
    • View In Article
    • CrossRef
29. Mak RH, Cheung W, Cone RD, et al. Mechanisms of disease: cytokine and adipokine signaling in uremic cachexia. Nat Clin Pract Nephrol. 2006;2:527–534
    • View In Article
    • MEDLINE
    • CrossRef
30. Lee SW, Russell J, Avioli LV. 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol: conversion impaired by systemic metabolic acidosis. Science. 1977;195:994–996
    • View In Article
    • MEDLINE
31. Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci. 2004;29:664–673
    • View In Article
    • MEDLINE
    • CrossRef
32. Mak RH. Effect of metabolic acidosis on insulin action and secretion in uremia. Kidney Int. 1998;54:603–607
    • View In Article
    • MEDLINE
    • CrossRef
33. Cannata-Andia JB, Gomez Alonso C. Vitamin D deficiency: a neglected aspect of disturbed calcium metabolism in renal failure. Nephrol Dial Transplant. 2002;17:1875–1878
    • View In Article
    • MEDLINE
    • CrossRef
34. Chen H, McCoy LF, Schleicher RL, et al. Measurement of 25-hydroxyvitamin D3 (25OHD3) and 25-hydroxyvitamin D2 (25OHD2) in human serum using liquid chromatography-tandem mass spectrometry and its comparison to a radioimmunoassay method. Clin Chim Acta. 2008;391:6–12
    • View In Article
    • CrossRef
35. White P, Cooke N. The multifunctional properties and characteristics of vitamin D-binding protein. Trends Endocrinol Metab. 2000;11:320–327
    • View In Article
    • MEDLINE
    • CrossRef
36. Fehrman-Ekholm I, Lotsander A, Logan K, et al. Concentrations of vitamin C, vitamin B12 and folic acid in patients treated with hemodialysis and on-line hemodiafiltration or hemofiltration. Scand J Urol Nephrol. 2008;42:74–80
    • View In Article
    • CrossRef
37. Vanholder R, De Smet R, Glorieux G, et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003;63:1934–1943
    • View In Article
    • MEDLINE
    • CrossRef
38. Gil C, Lucas C, Possante C, et al. On-line haemodiafiltration decreases serum TNFalpha levels in haemodialysis patients. Nephrol Dial Transplant. 2003;18:447–448
    • View In Article
    • MEDLINE
    • CrossRef
39. Van Tellingen A, Grooteman MP, Bartels PC, et al. Long-term reduction of plasma homocysteine levels by super-flux dialyzers in hemodialysis patients. Kidney Int. 2001;59:342–347
    • View In Article
    • MEDLINE
    • CrossRef
40. Beerenhout CH, Luik AJ, Jeuken-Mertens SG, et al. Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study. Nephrol Dial Transplant. 2005;20:1155–1163
    • View In Article
    • MEDLINE
    • CrossRef
41. Penne EL, Blankestijn PJ, Bots ML, et al. Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients—the Dutch convective transport study (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]. Curr Control Trials Cardiovasc Med. 2005;6:8
    • View In Article
42. Mandolfo S, Borlandelli S, Imbasciati E. Leptin and beta2-microglobulin kinetics with three different dialysis modalities. Int J Artif Organs. 2006;29:949–955
    • View In Article
    • MEDLINE